Mimi
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Probiotics Provoked D-lactic Acidosis in Short Bowel Syndrome: Case Report and Literature Review
WH KU, DCY LAU, KF HUEN
Metabolism of D-lactic Acid
When the condition of D-lactic acidosis was first described in human by Oh et al in 1979,2 it was thought that the metabolism of D-lactic acid is very slow in humans. Subsequent studies showed that healthy human subjects can metabolise D-lactic acid rapidly.30 The L-lactic acid is metabolised by the L-lactate dehydrogenase (L-LDH). Although humans do not possess D-lactate dehydrogenase (D-LDH), they can still metabolise D-lactic acid with the D-2-hydroxyacid dehydrogenase (D-2-HDH).31 The D-2- HDH is an intramitochondrial flavoprotein with highest activity in the kidney and liver. Experiments showed that in healthy human subjects, they can metabolise the intravenously or orally administrated D-lactic acid efficiently. However, when D- and L-lactic acids are present in high concentration they will cross inhibit each other's metabolism.31 D-lactic acidosis results from its overproduction and accumulation. The formation of organic acids during bacterial carbohydrate fermentation also inhibits the oxidation of D-lactic acid, which is prerequisite for its metabolism.31 These may explain why administration of D-lactic acid to healthy human subjects fails to produce D-lactic acidosis.
Mechanism of Neurological Manifestations
The neurological manifestations in D-lactic acidosis cannot be explained by the acidosis alone, as patients with acidosis resulting from other causes do not demonstrate the clinical features of D-lactic acidosis. In some patients with D-lactic acidosis the correction of acidosis with bicarbonate failed to improve the neurological symptoms. There are two proposed mechanism for the encephalopathy. The first one is the direct toxic effect of D-lactic acid to the brain.8,32 D-lactate can diffuse into the brain cells, causing decrease in intraneuronal pH, inhibits the pyruvate decarboxylation by the pyruvate dehydrogenase comlpex. Subsequently the production of acetyl CoA and adenosine triphosphate is impaired, resulting in altered neurotransmitter production. The cerebellum has particularly little reserve of pyruvate dehydrogenase complex, thus the cerebellar symptoms such as ataxia and slurred speech is prominent in D-lactic acidosis. The activity of pyruvate dehydrogenase complex is also impaired by thiamine deficiency. This may explain the difference in susceptibility to D-lactic acid in different subjects.
Clinical Manifestations of D-lactic Acidosis
Upon review of the patients in our case series, impaired mental status was a universal feature in D-lactic acidosis. Patients could present with confusion, stupor, or impaired conscious level ranging from somnolence, lethargy, drowsiness, to lost of consciousness and coma. There were cerebellar symptoms with ataxia, nystagmus, slurred speech and gait disturbance. Higher cognitive function impairment included aggressive behaviour, inability to concentrate, agitation, carbohydrate craving, "unhappy" and irritability. Other neurological manifestations were weakness, headache, bruxism and opisthotonus. The metabolic acidosis led to hyperventilation and tachypnoea. There were non-specific symptoms including nausea or pallor.
